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Science 16 August 1996:
Vol. 273. no. 5277, pp. 966 - 968
DOI: 10.1126/science.273.5277.966
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Reports

Protection Against Atherogenesis in Mice Mediated by Human Apolipoprotein A-IV

Nicolas Duverger, * Günter Tremp, Jean-Michel Caillaud, Florence Emmanuel, Graciela Castro, Jean-Charles Fruchart, Armin Steinmetz, Patrice Denèfle

Apolipoproteins are protein constituents of plasma lipid transport particles. Human apolipoprotein A-IV (apoA-IV) was expressed in the liver of C57BL/6 mice and mice deficient in apoE, both of which are prone to atherosclerosis, to investigate whether apoA-IV protects against this disease. In transgenic C57BL/6 mice on an atherogenic diet, the serum concentration of high density lipoprotein (HDL) cholesterol increased by 35 percent, whereas the concentration of endogenous apoA-I decreased by 29 percent, relative to those in transgenic mice on a normal diet. Expression of human apoA-IV in apoE-deficient mice on a normal diet resulted in an even more severe atherogenic lipoprotein profile, without affecting the concentration of HDL cholesterol, than that in nontransgenic apoE-deficient mice. However, transgenic mice of both backgrounds showed a substantial reduction in the size of atherosclerotic lesions. Thus, apoA-IV appears to protect against atherosclerosis by a mechanism that does not involve an increase in HDL cholesterol concentration.

N. Duverger, G. Tremp, J.-M. Caillaud, F. Emmanuel, P. Denèfle, Rhone-Poulenc Rorer, Gencell Division, Atherosclerosis Department, Centre de Recherches de VitryAlfortville, 13 Quai Jules Guesde-BP 14, 94403 Vitry sur Seine Cedex, France.
G. Castro and J.-C. Fruchart, INSERM 325, Institut Pasteur, 59019 Lille Cedex, France.
A. Steinmetz, Zentrum Innere Medizin, Endokrinologie und Stoffwechsel, Philipps-Universität, Marburg D-35043, Germany.
*   To whom correspondence should be addressed.


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